A variant in CYP2R1 predicts circulating vitamin D levels after supplementation with high-dose of vitamin D in healthy adolescent girls

Aim The determinants of serum vitamin D seems to be the environmental factors (dietary and supplementary intake and exposure to ultraviolet light) and genetic factors. We aimed to study the relationship between a vitamin D‐associated genetic polymorphism and serum 25(OH)D concentrations in healthy adolescent girls in Iran, and its effects on a high‐dose supplement of vitamin D. Material and method A total of 616 healthy adolescent girls with mean age 15 received 50,000 IU of vitamin D3 weekly over 9 weeks. Serum vitamin D levels and other metabolic factors were measured at baseline and after the intervention. The genotyping of the CYP2R1 variant (rs10741657) was performed by TaqMan genotyping assays. Results Regardless of the genetic background, at baseline, 87% of adolescent girls were vitamin D deficient (serum 25(OH)D level < 50 nmol/l). High‐dose supplementation with VitD reduced the proportion of girls who were deficient substantially to about 24%. The genetic analysis revealed that although at baseline there was not a gene‐vitamin D association ( p trend = 0.1), the response to supplementation appeared to be modulated by this variant ( p trend < 0.001). However, other anthropometric and biochemical measures were not affected by this intervention, over this short period. Serum 25(OH)D was increased in all participants although the carriers of the minor A allele seemed to be better responders so that the percentages of the change serum vitamin D in the holder of AA and AG genotypes were 539.4 ± 443.1 and 443.7 ± 384.6, respectively, compared with those with common GG genotype (363.3 ± 354.0). Our regression analysis revealed that the probability of an increase in serum 25(OH)D in a participant with AA genotype was 2.5‐fold greater than those with a GG genotype (OR = 2.5 (1.4–4.4); p value = 0.002). Conclusion Based on our findings, it appears that the rs10741657 variant of the CYP2R1 gene modulates the response to high‐dose of vitamin D supplementation.